9-1-09

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All rights reserved to text 8^th edition.

TYPICAL ANIMAL CELL

http://training.seer.cancer.gov/module_anatomy/images/illu_cell_structure.jpg

Structures: Golgi, Rough Endoplasmic Reticulum, Smooth Endoplasmic Reticulum, Plasma
Membrane, Secreted Product (Secretion), Secretory Vesicle, Lysosome, Small E. R. Vesicle,
Nucleus, Chromatin (DNA + protein), Nucleolus, Nuclear Pore, Mitochondrion, Centriolar
Microtubules, and Ribosomes (free ).

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CELLS - Chapter 3 of Marieb text, p. 61.

The cell theory was first put in writing by Oken in 1805, and later published by the botanist Schleiden and zoologist Schwann in 1839.  It stated that all living things were composed of cells. The term cell (in this context) was coined by the early microscopist Robert Hooke who looked at cork and saw openings that looked like monastery cells or rectangular rooms.

The Functions of Cells

To understand how cells relate to their environment, we will examine the mathematical concept of the relationship between cell surface area and volume.

Cell Size: most cells are from 10 micrometers to 100 micrometers (0.1mm) in diameter. The smaller cell dimensions are limited by the size of first the macromolecules like the nucleic acids and proteins of bacteria, and of the internal organelles (tiny organs) of larger cells. The larger cell dimensions are determined by the cell surface/volume ratio. As cell size increases, the cell's ability to gather nutrients and get rid of wastes from its environment decreases as the cell surface, exposed to the environment, decreases relative to the cell's volume.

Computation of surface/volume ratios,

PROKARYOTIC CELLS VS EUKARYOTIC CELLS

The term prokaryotic means "before a nucleus." It includes the bacteria. These organisms have a cell membrane (most important organelle for defining a cell, polysaccharide cell wall, and ribosomes composed of the nucleic acid RNA and DNA. The DNA is not inside a membrane-enveloped nucleus. They do not have membrane-bound organelles.

Eukaryotic cells have a nucleus, an outer plasma membrane and membrane-bound organelles. In the following pages learn the organelle name, function and be able to recognize the appearance of each.

See cells in action at http://www.cellsalive.com/index.htm .

TRANSPORT ACROSS MEMBRANES

Cell Membrane - p. 65-83 of the textbook.

Cell membrane is a fluid bilayer of phospholipids and globular proteins. Globular proteins that lie side by side and extend through the outer plasma membrane serve as facilitated transport channels for substances like glucose and amino acids. Other globular proteins will serve as active (energy expending) transport gated channels for ions like Sodium (Na⁺) and Potassium (K⁺). Many of the plasma membrane proteins have polysaccharides, glycolipids and protein chains projecting from its surface. Some serve as "cellular cement" for adhering to adjacent cells in a tissue layer. Other proteins allow for the recognition of cell type that is important for the immune system to recognize "self." A receptor may be an element of a transport channel. See below.

Many surface proteins serve as external membrane receptors for peptide hormones such as insulin, which causes the cell to increase its uptake of glucose from the extracellular fluid (ECF) by causing facilitated glucose (glut-4) transport channels to appear in the target cell's plasma membrane. The hormone insulin and its receptor have a lock and key relationship (insulin is the key), as do viruses and their receptor, and enzymes and substrates. There are G proteins in and adjacent to the membrane that act as second messengers (see chapter 18). Mutated genes can cause receptors to be absent, receptors may lose function, or the receptors may over-function. Disease results. Receptors also bind to neurotransmitters and lipoproteins.

Within the plasma membrane bilayer of phospholipids, cholesterol is embedded among the fatty acids tails of the cell membrane. It serves to stiffen the membrane by limiting the movement of the fatty acid tails of the phospholipids. Membrane not only covers the cell but also covers many of the internal organelles such as the nucleus, lysosomes and mitochondria. . Both the fatty acid tails and cholesterol, you remember, are nonpolar and hydrophobic, but they mix with each other. Water cannot stay in the interior if the membrane because it is polar. However, steroids hormones such as estrogen and testosterone are nonpolar, they will dissolve in and pass through the membrane.

Label the fluid mosaic model of the cell membrane.

                                                (Aliff drawing)

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Questions to Ponder 1.1.

1. Do a little research and see if you can find diseases of the following membrane channels:

            a. Epithelium chloride.

            b. Potassium channels in heart tissue.

            c. Potassium channels in neurons.

            d. Sodium channels.

2. Do a little research and see if you can find diseases of the following receptors:

            a. Androgen receptors (absent).

            b. Growth hormone releasing hormone (loss of function).

            c. Follicle stimulating hormone in females (absent).

            d. Thyroid stimulating hormone (gain).

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FLUID COMPARTMENTS IN THE BODY

What would happen if the blood plasma compartment had more water/less solutes than the extracellular compartment with less water/more solutes? Look up edema.

Types of Transport Between Fluid Compartments or From Air to a Fluid Compartment

Cell membranes are semipermeable (selectively permeable). Some small particles, such as oxygen and carbon dioxide, can enter or exit cells using their kinetic energy. The concept of semipermeability can be compared to the way a window screen serves its purpose. The screen is a passive filter, molecules of air and particles of dust may pass through it, flies and mosquitoes cannot.  If we modified our screen by giving it an electrical charge, it would repel particles of the same change and attract particles of the opposite charge, then it would be differentially permeable.

See p. 68-69.

Living membranes are differentially permeable: certain ions and molecules may enter or exit regardless of their size in many cases. See the sodium/potassium pump following. Generally, those materials pass through the membrane that are lipid soluble, sized appropriately, of the correct electrical charge, or have special channels. Some channels may be passive or actively gated channels in which entrance or exit of molecules is controlled by a gated channel.

Passive transport does not require any output of energy by a living cell. The energy of passive transport is kinetic.

A. Diffusion is the process of transport that uses kinetic energy to move molecules from areas of high concentration to areas of low concentration. All molecules move in straight lines and in random directions. As temperature increases, motion increases. Therefore, more molecules will move from higher concentration areas to lower concentration areas than move from low to high. Since the net movement of particles is from high to low, the particles move "down their concentration gradient." Can something purposeful be accomplished in a random movement? Sure! This is the way oxygen gets from inhaled air to the blood and on to the cells that need it. Carbon dioxide and ammonia wastes depart from cells by diffusion. Remember that the moving molecules do not "know" where they are moving, they just move randomly. Leak channels are passive channels for specific ions such as K⁺. See the Na/K pump illustration, below.

    The NaK-ATP-ase pump pushes Na⁺ ions out until there are 10-12 times more outside the cell than inside. Then it pumps K⁺ ions inside the cell     until there are 30 times more K⁺ inside than outside the cell. When ATP attaches a high-energy phosphate, the ATP-ase (the protein is an enzyme that hydrolyses ATP) protein channel changes shape to move the Na⁺ out; when the phosphate is removed, the protein gate reverts to its     original shape and moves the K⁺ in. Notice that after this pump runs for a while, the transport of ions is from a low concentration area to an area     of high concentration.

    Refer to the following diagram:

Start - Step 1 - phosphorylation (adding a high energy phosphate bond) of the protein pump (allows Na⁺ to attach by changing the shape of the protein. Na⁺ moves out)

                                                            Step 3 illustrates leakage channels.

Final State - where are most of the positive ions? Inside or outside? 

Are the steps 1 and 2 active transport of Na⁺ ions from low to high or high to low concentration areas? Is this also true for K⁺ ion movement? 

The membrane will hyperpolarize if additional cations are moved out or anions are moved inside.

Mutations of the genes that make Na-K-ATP-ase pump proteins of the heart lead to its failure.

Active Transport of Solids and Liquids

Endocytosis is a process that creates membrane bound vacuoles or vesicles (endosomes) formed at the cell surface and moved inside. Both the formation and movement of these vesicles requires the expenditure of ATP. The vesicles will be anchored to microtubules or microfilaments and moved through the cell by a ratcheting action described below. Also these vesicles may float freely in the cytoplasm as it moves (cytoplasmic streaming).  See p. 83 of textbook

Conversely, exocytosis  is a process that moves the contents of vesicles out of cells. The membrane bound vesicle will merge with the plasma membrane. Exocytosis occus in phagocytosis and when coated fat droplets (chylomicrocrons) are released from certain cells lining the small intestine. These fat droplets pass from the interstitial fluid, to lymph and on to blood.

Types of Endocytosis

a. Phagocytosis translates to "cell eating"- solid particles of food like bacteria are engulfed by immune cells called macrophages (translated "big eaters") in tissues or neutrophils and monocytes in the blood. Lysosomes (see below) fuse with a "food" vesicle that is formed and empty their powerful digestive enzymes.  A hapless bacterium is digested and its remains are removed by exocytosis.

b. Pinocytosis  literally means "cell drinking" - liquids are engulfed into ultramicroscopic vesicles. This is important for the absorption of the products of digestion.  In the kidneys, blood volume regulation through the reabsorption of water and solutes from the initial filtrate, and electrolyte balance is assisted by pinocytosis.

c. Receptor mediated endocytosis - low density lipoproteins (LDL's, packages of fat and cholesterol) are taken into cells by
receptor mediated endocytosis for use in metabolism, production of steroid hormones and membrane structure (and if they are taken in by liver cells, excretion). This is another lock and key process, the protein in the lipoprotein carrier serves as the key and a receptor on the surface of the target cell is the lock. Vessicles that form in plasma membrane may be coated with receptor proteins or not. The most common coating proteins are clathrin and caveolin. See p. 78.

When the liver cells (hepatocytes) process the lipids delivered by the chylomicron droplets, it repackages the fats and cholesterol into lipoprotein carriers.  VLDLs (very low density lipoproteins) are large droplets that carry fat and cholesterol in the blood. LDLs and HDLs split off from VLDLs.  As compared to VLDLs, LDLs have proportionally more cholesterol than fat.

Some LDLs contain oxidized cholesterol for excretion by the liver, perhaps in a special type of LDL. Although they are normally present in the blood, LDL's are called "bad cholesterol" because of their relationship to coronary artery disease.  LDL cholesterols play a role in the development of atherosclerosis, the formation of fat and cholesterol deposits in the walls of the coronary arteries of the heart and other locations. LDLs are engulfed by macrophages that crawl into the walls of arteries through lesions in the cells lining them. Oxidized cholesterol crystals are found in the buildup of fat, cholesterol, calcium deposits and collagen, collectively known as atherosclerotic plaque. Gases in cigarette smoke, viruses or bacteria, may make the lesions in the lining of the vessel that the macrophages crawl through. Also blood clots tend to form on the lesions; therefore, a clot plus the deposits in the arterial wall may block or occlude an artery. First, the heart muscle cells will be deprived of oxygen and nutrients, producing ischemia, and subsequent the heart muscle cells will die and decay, producing a lesion called a myocardial infarct.

Plaque deposits in coronary arteries may block the blood flow to heart muscle. HDL's (high density lipoproteins) are oxidized cholesterol scavengers therefore the "garbage trucks" of the blood. They carry the 'rancid' or oxidized cholesterol and normal cholesterol to the liver to be partially excreted with bile that is mixed into the digestive chime. Some of this cholesterol in bile will be used to emulsify fats, some will be reabsorbed by the small intestines, and some will be excreted in the feces. HDL's are called "good" cholesterol for this reason.

Normally, there is a ratio of LDL/HDL is 2.0 units or less/1. Higher ratios of >3/1 indicate increased risk for atherosclerosis. Your total cholesterol measure (<190 is good) is not as good information as an LDL/HDL ratio. The former can be done will a simple finger punch and blood blot. The latter must be done using blood drawn after overnight fasting. Anyone who has  an immediate member of their family die in the twenties or early thirties should have a fasting blood work performed by their physician. Heart disease is also related to a high intake of saturated fats and even high intake of fats in general, but inheritance plays a large role. Hepatocytes are directed by their genes to make a certain amount of lipoprotein carriers. But more importantly, genes of many cells make LDL receptors that are needed to put LDL-transported fat and cholesterol into cells. Familial hypercholesterolemia results from an inherited genetic defect in making these receptors.

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Questions to Ponder 1.2

1. If you have seen the classic movie, "The Blob," why can't single cells be as large as trucks?

2. Explain how, in a sedentary person, a diet high in simple carbohydrates, animal fat and salts contribute to the increase of diabetes mellitus seen in the U.S. and Canada.

3. Explain what would happen to blood pressure if the osmotic protein albumin was depleted by liver failure.

4. Criticize the media-invented term 'bad cholesterol' for LDL's.
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Membrane Bound Organelles - See p. 81 of text.

The term organelle for cells means "little organ." The nucleus is a large organelle covered by a double envelope of membrane that has small, single layered nuclear pores that allowing the passage of materials into (steroid hormones) and out (messenger RNA). The nucleus contains DNA either in thin strands or thickly coated with proteins as dense chromatin. The DNA contains the "messages of heredity" which dictate when and what the cell is to do or make. It is analogous to a master computer in a factory's main office that contains a library of blueprints and instructions for making different products. A nucleolus is a dark spot inside the nucleus that contains dense chromatin necessary for making ribosomal RNA and associated proteins. Before cell division (mitosis, see below) there are two nucleoli per cell, immediately after cell division there is one.

The Cell Factory at Work

Let's consider the beta cells in the endocrine glands of the pancreas, the islets of Langerhans.  Beta cells possess genes that direct the synthesis of the protein hormone, insulin. As we discussed in chapter 2, a gene with its DNA triplets can be transcribed into a messenger RNA polymer. 

The Steps of Transcription

1. The double stranded DNA will separate into two strands when the enzyme DNA gyrase breaks the hydrogen bonds, holding the nitrogenous bases together in a "rung" of the DNA ladder.

2. The enzyme RNA polymerase will join the appropriate reciprocal nucleotide to an exposed nucleotide on the strand to be copied - the sense strand. Remember that the A in a DNA triplet will bind to a U (uracil) in an mRNA nucleotide because RNA does not have T (thymine). So the DNA triplet ACT will transcribe to the mRNA codon UAC in messenger RNA. Please review the binding rules in chapter 2.

The Steps of Translation

1 The messenger RNA polymer formed, after some modification described in chapter 29, will leave the nucleus by moving through the single layer of membrane covering a nuclear pore. The modified mRNA is a copy of a gene or "blueprint" of the insulin product to be made by the cell factory.

2. The mRNA will attach to the small subunit of the ribosome, the "assembly line" of the cell factory. At this time the large subunit will join the complex. Ribosomes are made of ribosomal RNA and protein; they are the location of protein synthesis. Ribosomes may be "free" in the cytoplasm or adherent to the endoplasmic reticulum, a stack of hollow membranes, appearing much like a deflated balloon that has been folded.

3. Transfer RNA (tRNA) can pick up certain amino acids. There are 61 types of tRNA that can carry 20 amino acids. We will explore this aspect further in chapter 29. The catabolism of ATP charges each amino acid with the energy to make a bond with its tRNA. Transfer RNA has anticodons that bind reciprocally to the mRNA codons at the ribosome. Therefore the codon AAA will bind to the anticodon UUU. The amino acids then undergo dehydration synthesis, forming peptide bonds using the energy that originally came from ATP.

4. When all the codons have been translated, the mRNA will disassociate from the ribosome, and its small and large subunits will separate.

Endoplasmic Reticulum

There are two types:

a. Rough endoplasmic reticulum (rER) has ribosomes attached to its outer surface and it stores the proteins made at the ribosome.  The first protein to be made is not the final product, but preproinsulin that is a larger molecule. The pre- portion is a nonpolar "leader" sequence of amino acids that allows the protein to penetrate the largely nonpolar outer membrane of the rER. An enzyme inside the ER will cleave the pre- portion forming proinsulin.

The endoplasmic reticulum forms transport vesicles by a process that resembles the "budding" of yeast cells. A bubble-like structure will form from the ER membrane and detach. This transport vesicle is therefore a membrane-bound "fork lift" that carries proinsulin to the Golgi apparatus

b. Smooth endoplasmic reticulum (sER) is associated with the production of polysaccharides (glycogen) or lipids. Glycogen crystals form adjacent to the sER.

The Golgi Apparatus - see p. 85

The Golgi is similar to the endoplasmic reticulum, but it is larger and always smooth. It mixes enzymes with the collected proinsulin to be exported in larger secretion vesicles that bud off the outer trans face. Like "delivery vans," the secretory vesicles head from the factory warehouse to the distributor. Along the way, the pro- portion is cleaved. The secretory vesicles merge with the plasma membrane and deposite their final products (insuilin and the pro- sequence of amino acids) by exocytosis. The insulin made by our cell factory cell is now in the extracellular fluid and moves on to the blood to be distributed to target cells.

Lysosomes

Lysosomes are the so-called "suicide bags" of the cell. They form by budding from the Golgi apparatus. They are filled with a variety of enzymes that could destroy (hydrolyze) most materials in the cell. In fact, when cells die, these lysosomes burst and the cell undergoes autolysis (breaks itself down). When the amoeboid immune cells (macrophages and neutrophils) ingest bacteria or cell debris, lysosomes merge with a "food" vesicle made in phagocytosis and lyse its contents. Lysosomes can also take in and break down used organelles such as mitochondria. In the cell factory, lysosomes are "vacuum cleaners." 

In Tay-Sachs disease, an enzyme needed to break down certain neuronal membranes is absent because the genes that produce it are mutated. The cells then fill up with lysosomes filled with membrane layers. This is similar to fill garbage bags in your house without the ability to remove them.  Imagine being limited in moving around your house! 

Tay-Sachs is one of several storage diseases of cells that occur when one of the many lyosomal enzymes are absent. Certain useless materials in the lysosome build up instead of being normally broken down and the materials recycled.  Brain cells will gradually cease to function. Typically the baby is normal at birth, but then does nor progress in learning, eventually the child becomes vegetative and dies. There is no current treatment for TSD but the genes that produce the condition can be identified in the cells shed by a fetus. Other inherited lysosomal storage diseases, such as Gaucher's and Fabry's, may cause signs ranging from short stature and mental retardation, to kidney failure, stroke ere is no current treatment for TSD but the genes that produce the condition can be identified in the cells shed by a fetus.

In a miner's disease called silicosis and in asbestosis, mineral crystals may puncture lysosomal membranes, causing its enzymes to leak out into the cytoplasm. Lysosomal leakage is also implicated in rheumatoid arthritis and hypervitaminosis A (vitamin A weakens the membrane). Steroidal anti-inflammatory drugs strengthen lysosomal membranes and prevent leakage.

Peroxisomes

Peroxisomes are similar to lysosomes in that they are vesicles covered by a single membrane that encloses enzymes. However, they do not contain DNA and can replicate by a simple enlargement and division. The peroxisome's 14 enzymes include oxidases and peroxidases (e.g., catalase). The superoxide (peroxide) free radicals (see chapter 2), by-products of the oxidases, are detoxified there. Peroxisomes have a role in the catabolism (beta oxidation) of long chain fatty acids and the anabolism (synthesis) of cholesterol and the steroid hormones and bile acids derived from cholesterol. Inherited disorders include enzyme deficiencies (or lack thereof) and structural abnormalities that are metabolic in nature. Peroxisome enzyme deficiency is one of many causes of  "failure to thrive" in infants. Refsum disease is an inherited enzyme deficiency that causes cerebral ataxia (unsteadiness) and loss of vision (retinitis pigmentosum).  Phytanic acid, a common fatty acid in vegetables and dairy products, builds up in cells due to the absence of an enzyme that lyses it.

The Cell as a Factory

Mitochondria

 Mitochondria are the "powerhouses" of the cell. The ATP molecules made there are used for many activities including anabolism of proteins, lipids and carbohydrates; active transport, and cell movement. There are over 1000 mitochondria in an average cell. The mitochondrion has two membranes, an inner and outer. Anaerobic reactions occur just outside the mitochondrion. The reactions of the oxidative cell respiration (Kreb's Cycle) occur near and in the inner membrane. Most ATP is produced aerobically. Folds called cristae occur on the inner membrane. All mitochondria have DNA and all come from the mother's oocyte. 

Mitochondria are self-replicating. So far 13 genes have been discovered in mDNA: mutations of those genes cause mitochondrial cytopathies.  One rare type of epilepsy results from a mutation of mitochondrial DNA.  Epilepsy is an "electrical storm" of the brain. Neurons there depolarize and send electrical messages. If there are too many depolarizations, coupled with a lack of neural inhibition, over stimulation of the brain causes a loss of consciousness.  Another mDNA mutation causes Leber's optic neuropathy that causes blindness.

Cytoskeleton

A system of microtubules, anchoring proteins, myofilaments and the gel state of the cytoplasm allows a cell to have shape. The microtubules and myofilaments participate in movement of the whole cell and certain organelles. See below.

Microtubules

Microtubules assist in cell reproduction by moving and positioning chromosomes (containing DNA). Microtubules are composed of helically stacked tubulin protein molecules (polymers) to form multimers. Some microtubules have dynein or kinesin arms that are motor proteins that can ratchet in opposite directions.  These motor proteins attach to and push (ratchet) an adjacent microtubule in the opposite direction. The ratcheting is powered by the hydrolysis of ATP.  If the adjacent microtubule has an organelle or other structure attached to it (e.g., a chromosome), then the structure will appear to be moving in the cell. Moving vesicles are coated with motor proteins, so the organelle appears to be "walking" down a microtubule. We can think of some microtubules as being intracellular "highways."

http%3A%2F%2Fcellbio.utmb.edu%2Fcellbio%2Fmicrotubule_structure.htm

[[[[Drawing needed.]]]]

In the cell division of animal cells, microtubules "grow" from protein clouds immediately surrounding a bundle of nine triplets of microtubules (a 9 + 0 arrangement) collectively called a centriole. The protein cloud is called a microtubule organizing center or MTOC. After cell division, these microtubles disassemble. Some anticancer and other drugs, e.g., colchicines and taxol, interfere with the making or disassembly of microtubules, respectively. The result is a halt to the process of cell division. See below.

http%3A%2F%2Fcellbio.utmb.edu%2Fcellbio%2Fmicrotubule_structure.htm

Intermediate Filaments

Protein intermediate filaments are smaller than microtubules and contribute to a stable cell shape. They consist of a multimeric complex of tetrameres, four units that contain 4 protein helices to make a total of 16 helices per intermediate filament.

[[Insert drawing similar to:

Of many kinds of the "thick" filaments, we will discuss lamins, GFAPs, neurofilament proteins, keratin, vimentin and desmin.  Mutations of lamin genes result in a shortening of lamin fibers seen in cardiomyopathy.

Lamins help hold the nucleus in place and line the inner nuclear membrane. Lamins dissolve in prophase (see below), when the nuclear envelope dissolves, and reassemble in telophase, when the nuclear envelope reforms.  Mutations of the lamin-A gene on chromosome #1 cause aging disease (progeria) in children. Children usually die at age 13 of a heart attack or stoke. The defective gene results in a mutated, shortened lamin protein. As a result, progeric cells have lumpy, malformed nuclei. Also progeric chromosomal telomeres are abnormally short (see below). Either way, mitosis is affected.

(photo of progeric child and cells.))

 redraw?? ref: http://www.geneseo.edu/~mab5/edpage.html

GFAPs are found in glial cells of the brain. Too much GFAP production occurs in the cancer cells resulting from mutations of the genes that control GFAP production. Also when GFAP gene activity is over-expressed, globules of GFAP are found superimposed on the neurofibrillary tangles and plaques seen in Alzheimers disease (AD) neurological tissues.

Neurofilament protein is another category of intermediate filament.  These channel the growth of the thinner, cable-like distal extensions of neurons called axons. They also aid in axonal transport. The genes that produce neurofilaments are over-expressed in Parkinson's disease and the plaques amyotrophic lateral sclerosis (ALS: Lou Gehrig's disease).

(((Cell with florescent stain of neurofilaments.

Several types of keratin fibers fill up cells in the glassy layer of the skin (stratum lucidum). Above this layer, the cells are dead and scaly. Therefore, the upper layer of skin is called keratinized. There is an uncontrolled, over-expression of the genes that make keratin in many cancer cells. Psoriasis is a skin disease due to the cross-linking of keratin proteins.

Vimentin is an intermediate fiber found in the soft tissue cells - muscle, connective and neural. Vimentin filaments play a roll in the transport of cholesterol to the organelles involved in the synthesis of steroid hormones. The over-production of vimentin is a maker for soft tissue tumors.

Desmin is a protein filament found in muscle cells. The desmosome is a structure that binds cells together. Shown below is a desmosome that binds cardiac muscle cells together.

Microfilaments

Microfilaments are much smaller than microtubules. They consist of the contractile proteins actin (thin myofilaments) and the larger myosin (thick myofilaments) that are found in great abundance in muscle cells where they are called myofilaments.  Actin and myosin aid in cell movements and in the "pinching off" (cytokinesis) of two daughter cells in cell division. Myosin has ATP-ase "heads" that ratchet against the globular proteins in actin.  See below. We will take this subject up in greater detail in chapter 10.

See a French site of cell animations that include actin and myosin ratcheting at http://www.biomultimedia.net/archiv/muscle.htm

Locomotor Organelles

Locomotor organelles move cells such as sperms and they move mucus and cleaving embryonic cells on the surfaces of the respiratory and reproductory tracts, respectively.

1. Cilia

Cilia are numerous organelles covering most of the cells of the respiratory tree, the female Fallopian tube and some protozoa such as Paramecium. Cilia push dust and microbe contaminated mucus out of the lungs. Cilia have a whip like beating action and an inner "9+2" pattern of microtubules. Movement is accomplished by the ATP powered attachment of dynein arms of one outer microtubule pair to an adjacent pair, the dynein arms then pulling down "like climbing a ladder." At the origin of each cilium is a basal body, in which a 9-pointed star shaped protein called centrin lies proximal to the 9+0 group of microtubules. The inner two microtubules appear distally. The basal body includes an MTOC and the centrin may serve the same function as the bundle of microtubules in the centriole. It resembles growing large crystals starting with a tiny "seed crystal."

llustration.

The arrow in d indicates the centrin protein.

http://www.molbiolcell.org/cgi/content/full/14/7/2999/FIG3

When lungs are damaged by long-term inhalation of polluted air, such as cigarette smoke; the cilia that cover the cells lining most of the lung passages disappear. One of the first signs is a characteristic vigorous morning-cough that functions to remove secretions trapped in the bronchioles. These secretions limit flow of air to the air sacs where oxygen moves into the blood and carbon dioxide moves into the air to be exhaled. The smoker's hacking cough occurs in the day when they are smoking. This is caused when nicotine paralyses the cilia of the respiratory tree.

2. Flagella

Flagellae are whip-like structures that similar to structure to cilia, but larger. Some protozoan flagellae move with a corkscrew action and some with a propeller action. Prokaryote flagella have no microtubules.

Each sperm cell has one flagellum that moves in a propeller (rear) fashion. Distal to the head of the sperm is a mid-piece containing mitochondria that power the ratcheting of motor proteins arms as described above. If the genes that make dynein or kinesin are mutated, cilia and flagella will not function. For flagella, this would cause sperm cells to be immotile. For cilia, such a mutation results in the absence of motor proteins and primary ciliary dyskinesia (PCD), characterized by chronic pulmonary obstruction and infection.

3. Pseudopodia

Pseudopodia are the "false feet" that an amoeboid cell extends to capture "food." They may be fine, narrow extensions of the cell or more broadly shaped. Remember that the cytoplasm of colloidal mixtures of proteins in macrophages can undergo changes of state from a liquid sol stage to a semi-solid gel stage and accomplish movement. The cell extends a pseudopod by converting the interior of the extended arm to a gel while liquefying the trailing portion into a sol. A second reversal back to sol occurs at the leading edges of the pseudopod and sends sol streaming to the rear of the cell. These reversals of state (sol-gel) are controlled by pH changes and ATP powered movements of microfilaments.

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Questions to Ponder 1.3

1. An antibiotic, Rifampicin, binds to the ribosomes of bacteria irreversibly. Would the bacterium die immediately? Describe the processes in the bacteria that would be affected.

2. The organism that causes amoebic dysentery moves by extending one large pseudopodium and can be observed with red blood cells inside it. Describe its movement and what happens to the red blood cells.

3. Describe a storage disease involving microtubules.

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CELL DIVISION

Mitosis Overview - See  p. 98-100 of text .

Mitosis is a form of cell division that is accomplished in one division: one cell divides into two daughter cells. Mitosis is the most common form of cell division: it is used for replacing cells in organ such as the skin and stomach lining that constantly shed old cells. Some tissue cells lose the ability to do mitosis, generally speaking; e.g., neurons, skeletal muscle and cardiac muscle cells. The liver is an internal organ that can replace its hepatocytes after a disease like hepatitis. When the sperm cell fertilizes an egg, the resulting zygote begins the fist stage of the cell cycle, G₁. The dividing cells then will eventually produce a baby and a full growth adult.

First it is important to understand that, expecting cancer cells, most of an average cell's life is spent in activities other than mitosis. This is reflected in the cell cycle.

The Stages of the Cell Cycle

1. G₁ is the first growth and metabolic stage. It occurs after cell division, immediately following mitosis. It we use the example of a hapatocyte, then this cell is doing its normal functions. It energy and gene activity is causing the hepatocyte to make bile and detoxify certain chemical wastes. In G₁ the DNA strands are single. The 46 single chromosomes  (a single double helix of DNA) of a human cell cannot be seen with the light microscope.

2. The S phase follows G₁.  DNA synthesis and replication forms a second strand of DNA on a template or conserved strand. A double chromosome is formed. See chapter 2 and below.

3. G₂ is a second growth and metabolic stage; it immediately precedes mitosis. DNA strands are double in anticipation of distributing one set of genes to each daughter cell.

Notice that mitosis is only a small part of the cell cycle. G₁, S and G₂ are also referred to an interphase.

Types and Stages of Cell Division

Fission

Bacteria can reproduce by replicating a single chromosome, sending each strand resulting into a daughter cell.  This is similar to cloning in that usually the chromosomal genes are identical in both daughter cells. Bacteria have other genes in small loops of DNA called plasmids. You will learn how bacteria can do a form of sexual reproduction using these plasmids in a microbiology course.

Mitosis in Diploid Cells - See p. 97-100.

Diploid cells have two sets of chromosomes, a paternal and a maternal set. Mitosis requires only one cell division and the chromosome number stays the same from generation to generation.

Phases of Mitosis

1. Prophase initiates cell divison. Human somatic cells always begin prophase with 46 double chromosomes.

Steps

a.  Prophase begins when chromosomes become visible as they thicken and shorten. The DNA molecules become coiled and tightly would around histone proteins and become coated by non-histone prtoteins.  At this time the chromosomes are visible when viewed with the light microscope.

b.  Each centriole doubles in s phase to form a centrosome. The centrosome splits and the two resulting centrioles migrate to opposite poles of the cell. As the microtubules grow, the two centrioles are pushed away from each other.

3. The nuclear membrane disintegrates.

4. Microtubules form at the kinetochores and at the protein cloud surrounding the centriole - both are MTOCs. There are three types of microtubules directly involved in cell division:

            a. Centromeric (kinetochore) MTs extend from the centriole to the centromere.

            b. Polar MTs extend from centriole to centriole, crossing over the jumbled chromosomes to enclose a "spindle" of MTs.

c. Anchoring MTs (old = aster fibers) maintain the polar position of the centrioles by attaching to anchoring proteins in the plasma membrane.

            2. Metaphase occurs when the double chromosomes are lined up across the equator of the cell.

3. Anaphase: The Push-Pull Analogy

a. Polar microtubules appear to lengthen and thus their ratchetings push the opposite poles of the cell away from the center, this effect typically increases the diameter of the dividing cell from pole to pole. Polar microtubules assist in the push through the ATP-powered ratcheting action of motor proteins on adjacent polar microtubules.

b. The MTOC, the pericentriolar protein cloud can assemble the tubulin proteins of microtubules and thus lengthen them by assembly or shorten them by disassembly.

c. The centromeric M.T.s apparently shorten and pull the single chromosomes to each pole. Anaphase is easily recognized by the separation of the double chromosomes to make single ones. For the human liver cell, 46 d (double) chromosomes divide and 46 s (single) chromosomes go to each pole.

4. Telophase is recognized by the reforming nuclear membrane around the cluster of single chromosomes moved by microtubule ratcheting. Cytokinesis may begin in anaphase: this process pinches off the "waist" of the cell at the site of the former equator of the cell if the cell division is equal.

Chromosomes

Chromosomes are complexes of highly coiled DNA surrounded by proteins that cannot be seen in entirety with the light microscope until the prophase of cell division. Chromosomes get shorter and thicker as prophase continues. The DNA forms tight coils and loops around the histone proteins; other proteins, the nonhistones, form a covering of the coils and loops. The double chromosome consists 2 strands of DNA joined by a single centromere. Double chromosomes are always present in mitotic prophase and metaphase (see below). The centromere consists of 2 MTOCs called kinetochores.  A single chromosome has one centromere. The rule for counting chromosomes is to count centromeres, so one double chromosome is one indeed. Each strand of DNA is called a chromatid.

A double chromosome.

Karyotype

The human karyotype is a chart of the 23 pairs of chromosomes in a typical somatic or non-sex cell nucleus. White blood cells are cultured and arrested in late prophase of mitosis by the chemical colchicine that prevents microtubule formation. The pairs numbered 1 to 22 are call autosomes, pair number 23 are called sex chromosomes.

There are two X chromosomes for a female and X and y (much smaller) for a male.

When the chromosomes are stained, bands are displayed which help sorting the chromosomes correctly. Also the length of the chromosome and the position of the centromere are taken into account.

The two members of a pair are called homologous, meaning similar in structure. Genes that make certain proteins will occur in the same linear order normally in both homologous chromosomes. To illustrate, we will assume that we have two homologous single chromosomes. One chromosome can be referred to as paternal as it comes from the father of the individual from whom the cultured cells was taken. The matching homologous chromosome is called maternal. Normally if there is a genes for making enzyme a on one end of a homologous chromosome, an enzyme b-making gene in the middle, and an enzyme c-making gene on the other end, there is be a matching set of a, b and c genes on the homologous chromosome in the same linear order and in the same geographical position. Remember that if maternal and paternal a genes are mutated, then its enzyme product will not be produced and the individual will have an inherited illness such as lactose intolerance.

A karyotype is used to confirm the diagnosis of genetic diseases caused by gross chromosomal abnormalities. If three # 21 chromosomes are present, Down syndrome is indicated. Also chromosomes may have deletions or additions of genetic material that are observable. See p. 1102 of text.

Flourescing chromosomes in karyotypic arrangement at left, unarranged at right.

Types and Stages of Cell Division

Bacteria can reproduce by replicating a single chromosome, sending each strand resulting into a daughter cell.  This is similar to cloning in that usually the chromosomal genes are identical in both daughter cells. Bacteria have other genes in small loops of DNA called plasmids. You will learn how bacteria can do a form of sexual reproduction using these plasmids in a microbiology course.

Phases of Mitosis

Prophase initiates cell divison. Human somatic cells always begin prophase with 46 double chromosomes.

Steps

1.  Prophase begins when chromosomes become visible as they thicken and shorten.

2. A centrosome splits, the two resulting centrioles migrate to opposite poles of the cell. Each centriole doubles after G₁ to from a centrosome.  See www.cellsalive.com/cells/cellpix/spindle.gif .

3. The nuclear membrane disintegrates.

4. Microtubules form at the centrioles and the kinetochores. There are three types:

            a. Centromeric MTs extend from the centriole to the centromere.

            b. Polar MTs extend from centriole to centriole, crossing over the jumbled chromosomes.

c. Anchoring MTs (old aster fibers) maintain the polar position of the centrioles through anchoring proteins in the plasma

Draw Prophase - Include microtubules, centrioles and use 4 double chromosomes.

Metaphase: double chromosomes line up across center of cell.

Draw Metaphase:

2. Metaphase occurs when the double chromosomes line up across center of a cell.

Draw metaphase:

3. Anaphase: The Push-Pull Analogy

a. Polar microtubules appear to lengthen and thus push the opposite poles of the cell away from the center, this effect typically increases the diameter of the dividing cell from pole to pole. Polar microtubules assist in the push through the ATP-powered ratcheting action of motor proteins on adjacent polar microtubules.

b. The MTOC pericentriolar cloud can assemble the tubulin proteins of microtubules and thus lengthen or shorten them by disassembly.

c. The centromeric M.T.s apparently shorten and pull the single chromosomes to each pole. Anaphase is easily recognized by the separation of the double chromosomes to make single ones. For the human liver cell, 46 d (double) chromosomes divide and 46 s (single) chromosomes go to each pole.

 Draw Anaphase:

4. Telophase is recognized by the reforming nuclear membrane around the cluster of single chromosomes moved by microtubule ratcheting. Cytokinesis may begin in anaphase: this process pinches off the "waist" of the cell at the site of the former equator of the cell if the cell division is equal.

Draw Telophase:

MEIOSIS - see page 1032-1036.

The reason why sexual reproduction is seen in protozoa, algae and higher creatures is because it increases the genetic variety of the offspring. Every person carries some mutated genes. Reproducing with an unrelated mate will decrease the likelihood of those mutated genes from being expressed. Generally speaking, genetic outbreeding produces healthier offspring than inbreeding.

Meiosis is a form of cell division that prepares sex cells for fertilization. It is accomplished in two divisions and it reduces the chromosome number by 1/2. The definitions of phase of cell division are approximately the same as for mitosis, expect that the first division is designated meiosis I, and the second, meiosis II.

Spermatogenesis

a. The first division of meiosis is called the "reduction division" because the chromosome number is reduced by one half. In other words the one primary spermatocyte divides into 2 secondary spermatocytes, but the 2 resulting cells have 23 double chromosomes (in human) rather than the somatic cell content of 46. Meiosis must occur previous to fertilization in sexual reproduction. Why? Because the egg contributes 23 s and the sperm contributes 23s. That gives the baby 46s to begin G₁ of embryonic development (cleavage).

To illustrate the process generally, we will consider the formation of sperm - spermatogenesis. Cells reside in the testis that can do mitosis or meiosis. The mitosis of spermatogonia ("sperm eggs") is the reason why men can make sperms from puberty to old age. However, in metaphase of the first meiotic division (metaphase 1), 46d chromosomes of the primary spermatocyte divide into 23 d in each of two secondary spermatocytes.

b. In metaphase of the second division (metaphase II), 23s chromosomes are distributed to each spermatid that later develops into a sperm cell. This is actually a mitotic division. Why? The chromosomes number stays the same. We will take this up in more detail in chapter 27.

Oogenesis

See p. 1050-1051.

The meiotic formation of eggs or ova is a process of unequal cell division. The reduction division of the primary oocyte produces a large cell and a small first polar body. The first polar body is essentially a sac of 23d chromosomes that has to be jettisoned. The secondary oocyte likewise divides mitotically but equally, producing a mature oocyte and a second polar body of 23s chromosomes. The reason for the "wasting" of chroosmes is two fold: 1. The oocyte must keep its large size because it must contain all the cell organelles and energy to allow it to divide and survive for 6 days. At that time, a blastocyst, consisting of hundreds of cells but no larger than the original zygote, will implant in the lining of the uterus.

SPERMATOGENESIS VS. OOGENESIS

Oogenesis  unequal cell division  one large oocyte and two nonviable  polar bodies are produced from one oogonium	Spermatogensis equal cell division  four tiny sperms  produced from  one spermatogonium
m-RNA genes, stored energy resources,  organelles for the zygote  23 chromosomes all oocytes get large the larger x chromosome	No organelles contributed 23 chromosomes,  half of sperms get  the small y chromosome and half receive the larger x.

What would happen to the chromosome number of your great grandchildren if meiosis did not occur?

See the illustration below.

FERTILIZATION

Crossing Over

Parts of maternal and paternal chromosomes will break and rejoin to form new combinations of genes for the sex cells. This further increases the genetic diversity of offspring.  Crossing over occurs in prophase I of meiosis after homologous chromosomes pair-off in synapsis. A pair of homologous double chromosomes is called a tetrad. When the tetrad separates in diakinesis, parts of the individual strands of DNA or chromatids will break off and rejoin an adjacent chromatid from the opposite (maternal or paternal) chromatid.

_____________________________________________________________________________

Questions to Ponder 1.4

1. If bacteria can divide every 20 minutes, starting with one Salmonella (food poisoning) bacterium, how many would be present in your small intestine in 12 hours, assuming none die during that time?

2. For the following stages of mitosis and the cell cycle, fill in the correct number of chromosomes. Designate each set as 46 d or 46 s (double or single) as for a human skin cell. Remember to count chromosomes, count centromeres.

Prophase: ________________
Metaphase: _______________
Anaphase: ________________ (2 groups of ____ and ____ chromosomes)
Telophase: _______________ (as above, in each potential daughter cell)
G ₁ : ______________________
s: _______________________
G ₂ : ______________________
Prophase: ________________

3. For the following human spermatogonium and the spermatocytes derived from it, designate the chromosome numbers (d
or s) for each stage.

Prophase I: ____________________ (Primary Spermatocyte)
Metaphase I: ___________________...................................
Anaphase I: ____________________ (in each daughter cell to be)
Telophase I: ___________________ (in each daughter cell to be)
Prophase II: ___________________ (Secondary Spermatocyte)
Metaphase II: __________________
Anaphase II: ___________________ (in each daughter cell to be)
Telophase II: __________________ (in each daughter cell to be)
Mature Sperm Cell: _____________
Mature Ovum: ___________________
Zygote = Sperm # + Ovum # = ____________________ (G₁ cell cycle phase of zygote)

4. What would happen to the chromosome number of your great grandchildren if meiosis did not occur?

5. Explain the following statement: "Mitochondrial cytopathies are always passed from mother to child."
_____________________________________________________________________

For an online learning program on mitosis the Biology Project - Cell Biology from the University of Arizona, go to http://www.biology.arizona.edu/cell_bio/cell_bio.html .

            Causes of DNA/Gene Mutation

1. Radiation - gamma rays, X-rays, ultraviolet rays, beta-rays (electrons) and neutrons can make abnormal nucleotides and bonding patterns in DNA. Specifically, UV-B makes bonds between thymine bases (thymine dimers) that are adjacent "vertically" in the DNA ladder. Beta rays and neutrons are also mutagenic.

2. Viruses insert their DNA or the DNA made from viral RNA into the chromosomes of their host cell. If a viral genome (assortment of genes) is inserted into a human chromosome, oncogenes may result. Most oncogenes are mutated forms of tumor suppressor genes that control mitosis, e.g., BRCA 1 and 2, or genes that cause apoptosis of abnormal cells expressing mutations. Inherited mutant genes can result in cancer include mutant BRCA-1 and -2 that greatly increase the risk of breast cancer, the retinoblastoma gene, and the mutant p53 that is implicated in most cancers including colon and cervical. It is possible that x-rays can precipitate the final mutation of some oncogenes.  Here inheritance of a defective BRCA plays a role. Most mutations that produce disease are actually a series of mutations. One study showed that stage 2 brain cancer cells had fewer mutations than stage 3 cells, and so for stage 4. The k-ras mutation is stimulated by estrogen that acts as a mitogen to increase the rate of mitosis of tumor cells. Viral genes that are considered proto-oncogenes include proto-abl, -ras and -onc.

The normal p53 gene causes cells to die if they are too old or are defective. When cells expire, they burst open, hence the name for the process is apoptosis. However, cancer cells are immortal. There are worldwide cultures of breast cancer cells taken from a woman who died of breast cancer in 1968 - they are still thriving as long as the cultures are fed and cleaned.

The National Institute of Environmental Health Sciences and the National Toxicology Program recognizes viruses as carcinogens. These include Hepatitis B and C that cause liver cancer, and human papilloma viruses that cause cervical cancer.

3. Mutagenic chemicals - polycyclic aromatic hydrocarbons (benzopyrenes: MeIQ, MeIQx, and PhIP), the benzene that is in high test gasoline, asbestos, PCBs and PCPs, and vinyl chloride are notorious carcinogens.  Diethylsylbestrol was a synthetic estrogen used in the 1960s and 1970s to treat post-menopausal estrogen deficiencies. It not only caused cervical cancer in the women that took it, but also their children. Benzopyrenes are liquids that can be distilled from the smoke of cigarettes, grills, and other incompletely combusted organic hydrocarbons. In the 1960s, benzopyrenes were used to cause tumor growth on the skin of experimental animals. The National Toxicology Program recognizes smoked and smokeless tobacco as carcinogens.  In the 1970s, vinyl chloride caused liver cancers in many workers in facilities that manufactured vinyl for plastics.

Mitogens are substances that increase the rate of cell division. Nicotine is not a mutagen, but it is a mitogen. Mitogens such as nicotine, testosterone and estrogen increase the frequency of mistakes in copying DNA and/or increase the number of mutant genes in the resulting cells. The steroid hormones estrogen and testosterone are, respectively, mitogens for breast cancer cells and prostate cancer cells.

4. Mistakes in replication of genes/DNA: Indirectly, increasing the rate of mitosis of cells can lead to mutations that could cause cancer. When physicians observe hyperplasia (abnormal growth) in normal tissues, they consider the condition to be "precancerous." Asbestos and wood dust (surprisingly) are carcinogens but the mechanisms of mutation are not definitely known. However since these provide a constant irritation that produces hyperplasia, the mutagenic effect certainly includes mistakes in replication. Synergism (interaction) with other mutagens may also be a factor.

Aging of Cells

     [[[[from Art Explosion]]]]

The Causes of the Aging of Cells

Programmed cell death and malfunctions occur during aging.

For cells the causes of aging include:

1. Programmed cell death and malfunctions are natural processes. Also viruses can cause changes in cells that lead to their normal self-destruction by apoptosis. Why do humans live 70+ years and dogs only 12+? It is certainly not because dogs don't get enough sleep!

The current theory asserts that there is a gene-controlled limitation on the number of times a given cell can do mitosis (the Hayflick limit), although there are fibroblast cells that may have unlimited potential. One problem with the gene-limit to cell division is that the number of divisions that cultured cells undergo generally exceeds the life span of the organism from which the cells were taken. Also when older cells are moved into younger organisms, they divide normally and the life span of the recipient is not shortened.

But genes are certainly involved in aging even if we don't understand very well how they produce declining functions such as endocrine hormone secretion.

2. Accumulation of mutations from background radiation, radioimaging, chemical exposure, and mistakes in replication will cause cells to

age and cell metabolism accordingly slows; e.g., the velocity of neuron conduction slows with advancing age. A theory that blends with this one, suggests a decline DNA repair functions. If the genes for making the enzymes that repair DNA are mutated, then the repair function will be affected. The accumulation of mutations in mitochondria will reduce ATP production in a cell. There may be mutations or other changes that result in the insensitivity of membrane or nuclear receptors to endocrine hormones. Also the receptors may be altered by mutation or glucose cross-linking of membrane proteins.

3. Accumulation of wastes ("clinkers") in cells such as lipofuscins affect cell function. When I was a kid I used to shovel clinkers, brown chunks of glassy material, out of my grandmother's coal-burning furnace. Obviously, if the clinkers were not shoveled out, one could not get any more fuel in the furnace to burn. Something approaching that may occur due to the buildup of lipofuscins, yellowish-brown lipids or proteinaceous chemicals, that cells can't dispose of.  Lysosomes become dysfunctional when they are filled with lipofuscins. Cells filled with clinkers become senescent and slow function; e.g., neuron conduction velocity slows with advancing age.  These wastes are the by-products of the lysosomal and peroxisomal oxidation of certain fats by free radicals or peroxides. Clinker theory is also linked to the free radical and superoxide theory of aging. In 1968, a study was done of enzymatically-digested cadavers. It showed lipofuscin buildup directly proportional to the age of the cadaver.

4. Loss of telomeres that cap the ends of chromosomes leads to the death of the cell. Cells cannot reproduce without these chromosomal caps. Pieces of telomeres are lost very gradually over many mitotic cell divisions. This may explain the Hayflick effect. But embryonic and, regrettably, cancer cells use an enzyme called telomerase that rebuilds telomeres! Cancer cells are immortal. They are also like embryonic cells in that they divide rapidly and migrate to new locations. Therefore, the discovery of telomerase and telomeres does not necessarily lead to human immortality. If abnormal cells marked for apoptosis acquired telomeres, they would have a strong chance of becoming cancerous.

Critical Thinking

1. Criticize the term "bad cholesterol" for LDLs.

2. Explain the relationship between cigarette smoking and cancer in the lung and colon.

3. Who contributes more genes to a male offspring, mom or dad or are the contributions the same? Explain your answer.

4. Why is cancer more prevalent in older people?  Similarly, why has cancer increased generally in all age groups over the 20th century?

Cyber Surfin'

See great graphic and photo images of cells in action at Cells Alive! - http://www.cellsalive.com/index.htm .

For more detail about organelles and their physiology, see http://library.thinkquest.org/12413/structures.html

From Biology Multimedia in France, see cell animations that include actin and myosin ratcheting at http://www.biomultimedia.net/archiv/muscle.htm.

For an online learning program on mitosis and meiosis, see the Biology Project - Cell Biology from the University of Arizona. Go to http://www.biology.arizona.edu/cell_bio/cell_bio.html .

The Howard Hughes Medical Institute's Bio-Interactive has a great site for cell biology, e.g., sex determination and the y chromosome at

www.hhmi.org/biointeractive/lectures

Review of Important Concepts

Cells

                        I.  The cell theory of Oken, Schleiden and Schwann stated that all living organisms are composed of cells.

                        II. The Function of Cells

                                    A. The cell volume/area ratio decreases as cells get larger.

                                                1. This decreases the area available for transport of materials into and out of the cell.

                        III. The Structure of Cells

                                    A. Prokaryotic cells do not have a nucleus or other membrane-bound organelles.

                                    B. Eukaryotic cells have a membrane-bound nucleus and other membrane-bound organelles.

                        IV. Transport Between Fluid Compartment or from Air to a Fluid Compartment

                                    A. Fluid Compartments in the Human Body.

                                                1. The extracellular compartments include blood plasma and interstitial fluid.

                                                2. The intracellular compartment resides inside cells.

                                    A. Transport Across Membranes

                                                1. The cell membrane is a fluid bilayer of proteins and phospholipids.

                                                2. Proteins of the cell membrane include receptors.

a. Membrane receptors can bind to peptide hormones, lipoprotein carriers, neurotransmitters and viruses.

b. Membrane receptors may be parts of channels for ions and molecules.

                                                3. Membrane proteins include channels and gated channels for ions and specific molecules.

4. Plasma membrane proteins have polypeptide chain, glycolipid and carbohydrate molecules that serve as cellular cement and cell recognition proteins that are important in immunity.

5. The plasma membrane is semipermeable, basically screening molecules according to their size.

                                    B. Types of Transport

                                                1. Passive transport occurs due to the kinetic energy of small particles.

a. Diffusion is the process in which molecules move passively from a high concentration area to a low concentration area.

b. Oxygen, water, carbon dioxide and ammonia are common molecules that move into and out of cells by diffusion.

            1.) Leak channels are diffusion channels through which a specific ion (potassium) diffuses.

c. Osmosis is a special type of diffusion in which only water molecules diffuse through a semipermeable membrane.

            1.) The terms of tonicity compare the solute and solvent concentrations of two solutions.

a.) A hypotonic solution is one with a lower concentration of solutes and a higher concentration of solvent (water molecules) as compared to another solution. Pure water is always hypotonic to cells.

b.) A hypertonic solution has a higher concentration of solutes and a lower concentration of solvent as compared to another solution.

1.)) Osmotic pressure in a force developed by water moving from a hypotonic solution to a hypertonic solution. Naturally, water moves toward higher solute concentrations.

2.)) Bulk flow of water (solvent drag) accompanies the active transport of solutes. As solutes are moved by cells, water molecules are "dragged" passively.

3.)) Reverse osmosis is a process that is used to purify water by applying a physical force that exceeds the osmotic pressure.

c.) Isotonic solutions have equivalently equal concentrations of solutes and solvent. A 0.85% NaCl solution is 8.5 g/liter is called normal saline because it is isotonic to blood plasma as is a 5.1% glucose (dextrose) solution.

d. The kidney dialysis machine uses a plastic semipermeable membrane to remove urea from a patient's blood plasma to a bath solution that is slightly hypertonic. Walking dialysis applies the patient's own abdominal membranes (mesenteries) to filter wastes into a bath solution placed into the abdominal cavity.

e. Facilitated diffusion occurs when specific molecules move through "dedicated" channels.

a.) The operation of the glut-4 channels for glucose is an example. The glucose must fit the channel to pass through.

2. Active transport occurs when the cell must expend energy (ATP) to transport the particles from a low concentration area to a high concentration area.

a. The sodium-potassium pump maintains a higher concentration of sodium ions outside cells and a higher concentration of potassium inside cells.

a.) When ATP breaks down, its high-energy phosphate and bond attaches to the inner pump protein, pumping out 3 sodium ions.

1.) The Na/K pump maintains the proper concentration of the osmotically active Na⁺ and K⁺ ions in intracellular (high K⁺, low Na⁺) and extracellular (high Na⁺, low K⁺) fluids.

b.) When the now, low energy phosphate detaches, 2 potassium ions are transported inside.

c.) Subsequently potassium leak channels will allow more K⁺ out of the cell.

1.) K⁺ cation leakage increases the polarity of the membrane.

                                                            b. Endocytosis is a process that actively transports solids and liquids into cells.

                                                                        a.) Membrane bound vesicles form in the plasma membrane.

b.) Exocytosis is the reverse of endocytosis, it is important in moving fat droplets (eventually) into the blood.

c.) Types of endocytosis include:

1.) Phagocytosis begins when a solid particle (bacterium or cell debris) is engulfed by cytoplasmic extensions called pseudopodia.

a.)) Lysosomes fuse with the "food" vesicle formed and empty powerful enzymes into it.

b.)) The solid particle is chemically digested.

c.))) Waste particles are removed by exocytosis.

d.)) Common phagocytes include macrophages in tissues and neutrophils and monocytes in blood.

2.) Pinocytosis forms fluid-filed vesicles in the plasma membrane.

a.)) Pinoctosis allows for the absorption of the products of enzymatic digestion and the reabsorption of important solutes in the kidney filtrate

3.) Receptor mediated endocytosis is a process of taking materials into cells after a lock and key binding of surface protein of the particle (e.g., virus) or lipoprotein carrier to a specific receptor on the plasma membrane of a target cell.

            a.)) Lipoprotein carriers carry neutral fat and cholesterol dissolved in it to cells.

1.)) Cholesterol is used to build steroid hormones and cell membranes. Fat is used for making ATP or storing energy.

2.)) Chylomicrons are taken up by liver cells.

3.)) The liver cells repackage the fat and cholesterol into large VLDLs.

4.))  VLDLs split into HDLs and LDLs.

5.)) LDLs carry fat and cholesterol to certain cells.

6.)) HDLs carry fat and oxidized cholesterol back to the liver.

7.)) Familial hypercholesterolemia is due to an inherited defect of LDL receptors on liver cells.

8.)) Some cholesterol is excreted, moving first into liver bile and into feces.

V. The Organelles of Cells

A. The term organelle means "little organ."

B. The nucleus is a large organelle that contains chromosomal DNA in the form of strands or dense chromatin.

            1. The nucleolus is an area of dense chromatin that makes ribosomal RNA (rRNA).

C. The central dogma of DNA action states that DNA can direct protein synthesis (from chapter 2) and replicate genes.

1. Transcription is the process in which genes are transcribed by RNA polymerase to form messenger RNA (mRNA), which is a copy of the gene.

            a. Triplets of DNA on a sense strand are copied to mRNA codons.

                        a.)) A in DNA binds to U in mRNA.

b. After some modification, the mRNA departs the nucleus through a nuclear pore.

2. Translation is the process of the formation of a protein by the dehydration synthesis of amino acids at the ribosome.

            a. mRNA attaches to the small subunit of the ribosome.

            b. The large subunit joins the small subunit to make a functioning ribosome.

c. Transfer RNAs (tRNAs) bring amino acids to the ribosome, one at a time.

a.)) The amino acid molecules have been previously charged with bonding energy by the hydrolysis of ATP.

b.)) tRNA carries an anticodon that binds to the mRNA codon as one amino acid is brought to the ribsome.

c. The amino acid molecules join by dehydration synthesis that forms peptide bonds and a protein molecule

d. After translation, the mRNA detaches from the ribosome and the two subunits separate.

e. The first protein made in the translation of the gene for insulin is preproinsulin.

                                                            D. The endoplasmic reticulum (rER) is a stacked, connected series of hollow membranes.

                                                                        1. The rough endoplasmic membrane has ribosomes attached to its outer surfaces.

a. Preproinsulin has a pre-portion that serves as a nonpolar "leader" for penetrating the outer surface of the rER.

b. Preproinsulin encounters an enzyme that cleaves the pre- portion.

c. Proinsulin is present in small transport vesicles that bud off the rER and move to the Golgi.

                                                                        2. Smooth endoplasmic reticulum (sER) dies not have attached ribosomes.

                                                                                    a. The sER is associated with the production of lipids and carbohydrates.

                                                            E. The Golgi apparatus is similar to sER but larger.

                                                                        1. Proinsulin is mixed with enzymes there.

                                                                        2. Secretion vesicles are formed by "budding" from the Golgi.

                                                                        3. Secretion vesicles merge with the plasma membrane, releasing insulin into the extracellular fluids.

                                                                        4. Endocrine cells that secrete hormones have prominent Golgi apparati.

                                                            F. Lysosomes form by budding off the Golgi. They stay inside the cell.

1. Lysosomes contain a variety of powerful digestive enzymes that can digest most materials in the cell.

a. Lysosomes engulf and digest malfunctioning mitochondria.

b. Lysosomes merge with food vesicles to digest viruses, bacteria or cell debris.

c. When cells die, the lysosomes eventually rupture and the cell digests itself (autolysis).

d. If a lysosome lacks an enzyme, undigested materials accumulate in lysosomes causing cells to malfunction.             

a.)) A storage disease results when a gene mutation results in the absence of a lysosomal enzyme.

1.)) Tay-Sachs disease causes a baby who appears normal at birth to gradually become vegetative over a period of several years.

2.)) Neurons in the brain malfunction due to the accumulation of membrane-filled lysosomes.

G. Peroxisomes are similar to lysosomes but do not contain DNA.

1. Peroxisomes replicate by a simple enlargement and division.

            2. They denature peroxides using catalase.

            3. Peroxisomes oxidize long-chain fatty acids using oxidase enzymes.

            4. They help synthesize cholesterol and the bile acids derived from it.

            5. Storage diseases result from gene mutations.

                        a. Refsum disease is one cause of failure to thrive in infants.

                        b. RD is due to the buildup of phytanic acid (a fatty acid) in cells.

H. Mitochondria - there are 1000-2000 in a typical cell.

            1. Each mitochondrion has a small loop of DNA.

                        a. Mitochondria can replicate.

b. All mitochondia come from the oocyte.

            2. Mitochondria make ATP from the catabolism of glucose (see chapter 2).

                        a. Anaerobic glycolysis occurs just outside the mitochondrion.

                        b. Aerobic breakdown of glucose residues occurs inside the mitochondrion.

c. Typically the oxidation of 1 molecule of glucose can make a net production of 34 ATPs and carbon dioxide and water byproducts.

d. Mutation of mitochondrial genes results in mitochondrial cytopathies.

            a.)) Rare forms of blindness and epilepsy result.

            b.)) Mitochondrial cytopathies are always passed from mother to child.

I. Cytoskeleton consists of microtubules, microfilaments and the gel state of cytoplasm.

1. Microtubules serve to support cell structure and act as highways to move organelles and chromosomes around the cell.

            a. A microtubule is a helical mulitmeric protein composed of tubulin monomers.

a.)) Microtubules grow from a protein cloud (microtubule organizing center) surrounding a 9+0 bundle of microtubules.

b.)) The microtubule organizing center and microtubules is a centriole.

c.)) MTs may be coated with the motor proteins dynein and kinesin.

d.)) Microtubules can ratchet against each other to move chromosomes in cell division.

e.)) Vesicles coated with motor proteins can

"walk" down a microtubule                                                                                       

2. Microfilaments consist of the thin fiber actin protein and the thick fiber myosin protein.

                                                                                                a. In muscle cells actin and myosin are called myofilaments.

                                                                                                            a.)) The heads of myosin ratchet against the G proteins in actin.

1.)) Actin and myosin assist the process of cytokinesis or pinching off the waist of a dividing cell.

2.)) The ratcheting of myosin against actin produces muscle cell contration and assists other cell movement.

                                                                        J. Locomotor organelles move cells or materials on cells.

1. Cilia are small whip-like organelles that are important for moving oocytes and the post-fertilization, cleavage stages of embryos in the Fallopian tubes.

a. Cilia move mucus in the nasal cavities and the respiratory tree.

b. Air pollution causes the loss of ciliated cells in the respiratory tree.

                                                                                                c. Nicotine paralyses cilia.

                                                                                                d. Cilia have a 9+2 organization of microtubules and ratcheting motor proteins.

e. Mutation of the genes that make the motor proteins of cilia causes chronic pulmonary obstruction and infection.

2. A flagellum is larger, whip-like organelle that, using a propeller motion, moves a sperm cell through the female reproductory tract.

            a. A flagellum also has a 9+2 pattern of ratcheting microtubules.

b. Mutation of the genes that make the motor proteins of flagella causes sperms to be immotile.

3. Pseudopodia are extensions of plasma membrane and cytoplasm that can surround and engulf solid materials (phagocytosis) and cause movement.

            a. They are the locomotor organelles of the amoeboid immune cells.

b. Sol-gel reversals and the ratcheting of myosin against action cause the formation of pseudopods.

                                                VI. Cell Division

A. The Cell Cycle consists of phases involving normal metabolism including growth and cell division.

            1. G₁ is the first growth and metabolic stage that immediately follows cell division.

                        a. The human chromosome count at this stage is 46 single chromosomes.

a.)) A single chromosome has one strand of DNA (chromatid) and one centromere.

            2. In the s or synthesis phase, DNA replication takes place.

a. Single chromosomes become double chromosomes, each one of which has one centromere.

                                                                                    3. G₂ is the second growth and metabolic stage.

b. The human somatic cell count in G₂ is 46 double chromosomes.

a.)) Each double chromosome has one centromere and two chromatids.

B. Karyotyping is a technique for the sorting homologous double chromosome pairs of a eukaryotic organism.

1. Chromosomes are sorting by length, centromere position, and banding.

2. The human karyotype has 46 pairs of chromosomes.

a. Chromosome numbers 1-22 are called autosomes.

b. Pair number 23 are the sex chromosomes, the larger X and smaller y.

            a.)) The smaller y chromosome normally determines the sex as male.

b.)) The SR-Y gene signals certain genes on the  X-chromosome to cause the male pattern of organ development.

c.)) Mutating certain NR-Y genes on the y chromosome results in infertility.

d.)) Mutating certain genes that produce male hormone receptors will produce an x-y male that externally looks like a female.

C. Fission occurs when a single chromosome is replicated as the bacterial cell divides.

D. Mitosis the process of cell division used in human growth and the replacement of cells.

                                                                                    1. Mitosis is accomplished in one cell division: that is, one cell divides into two.

                                                                                                a. Chromosome number stays the same before and after mitosis.

a.)) Mitosis ensures that the daughter cells get the same compliment of genes that the original cell had.

b.)) Human somatic cells generally have 46 chromosomes.

                                                                                                b. Mitosis occurs in stages.

a.)) To begin prophase, chromosomes become apparent in the light microscope.

1.)) The double chromosomes thicken and shorten as the coiled DNA is wrapped around histone proteins and becomes coated by non-histone proteins. See chapter 2.

                                                2.)) The nuclear membrane distegrates.

                                                3.)) The centrosome splits into two centrioles.

4.)) The centrioles are moved towards opposite poles of the cell; the growing microtubules push the centrioles apart.

                                                5.)) The chromosomes are moved to the equator of the cell.

b.)) In metaphase the double chromosomes line up across the equator of the cell.

            1.)) The polar microtubules stretch from centriole to centriole.

2.)) The centromere consists of two kinetochores that serve as MTOCs for the centromeric MTs..

3.)) The centromeric (kinetochore) MTs grow from the protein cloud of the centriole.

4.)) The anchoring MTs grow from the protein cloud of the centriole and attach to anchoring proteins in the plasma membrane.

c.)) In anaphase the double chromosomes are pulled apart by the shortening and ratcheting centromeric MTs.

            1.)) Cytokinesis usually begins in anaphase. See above.

            2.)) This results in two groups of 46 single chromosomes.

3.)) Chromosomes move to the opposite poles of the cells.

4.)) The polar microtubules push the poles of the cell apart, causing the dividing cell to increase in diameter.

d.)) In telophase the nuclear membrane begins to form around each group of 46s chromosomes.

1.)) Cytokinesis comes to completion.

2.)) The daughter cells enter G₁ of the cell cycle.

E. Meiosis is type of cell division that prepares sex cells for fertilization and increases the genetic variety of offspring.

            1. Meiosis requires two cell divisions.

a. Meiosis I is a reduction division that decreases the chromosome number by 1/2 - in humans 46d à two cells each containing 23d.

b. Meiosis II is a mitotic division: 23d à two cells of 23 s.

c. Spermatogenesis are equal cell divisions that produces four cells with 23s chromosomes each after the completion of Meiosis II.

a.)) A primary oocyte with 46 chromosomes divides into two secondary oocytes each with 23d chromosomes

b.)) Each secondary oocyte dives into two cells with 23s chromosomes.

c.)) Spermatogonia divide mitotically to maintain sperm production or become primary spermatocytes.

d. Oogenesis is an equal cell division in which a first polar body (pseudocell) removes 23 d chromosomes from the primary oocyte, and the second polar body removes 23s chromosomes from the secondary oocyte.

a.)) Oocytes retain the large energy resources and organelles needed to support the post-fertilization embryo until it implants in the endometrium.

e. Crossing over moves genes from a maternal double chromosome to the paternal chromosome and vice versa.

a.)) Synapsis occurs when the maternal and paternal chromosomes pair off in the prophase of Meiosis I.

b.)) The complex of two double chromosomes is a tetrad.

c.)) Pieces of chromosomes break and rejoin in recombination.

d.)) Recombination of genes increases the variety of gene assortments in oocytes and spermatocytes.

VII. Cancers are caused by a series of gene mutations, particularly in the genes that control mitosis, specifically the tumor suppressor genes.

            A. The causes of gene mutation include atomic radiation, viruses, chemicals and mistakes in replications.

1. The forms of atomic radiation that are mutagenic include neutrons, beta particles (electrons), alpha particles (helium nuclei), gamma rays, X-rays, and ultraviolet rays.

2. Many viruses insert their DNA or a DNA copy of their RNA genome into the DNA of host cells.

            a. An oncogene is a cancer-producing gene that can be inherited.

            b. Certain viral genomes contain the proto-oncogenes proto-onc, -ras, and -abl

3. Certain chemicals are known to mutate DNA including PCBs, PCPs, vinyl chloride, benzopyrenes, benzene.

4. Mistakes in the replication of DNA incorporate mutated genes that either result in the senescence and death of the cell or cancerous changes.

                                                VIII. The aging or senescence of cells causes a gradual loss of function.

A. The causes of cell aging are programmed cell death by apoptosis, accumulation of mutations, accumulations of "clinkers," and loss of telomeres.

            1. Normally cells that cannot conduct mitosis will become senescent and die by apoptosis.

            Also, cells with mutated genes normally undergo apoptosis.

                        a. Genes normally limit the number of times cells can do mitosis.

            2. In the life of an organism, mutations from background radiation and chemical exposure occur.

                        a. Mistakes in replication also accumulate.

b. The accumulated mutations of cells cause a slowing of metabolic functions such as growth.

3. Accumulation of clinkers that are the byproducts of lysosome and peroxisome oxidation of fats by peroxides and free radicals, cause cell metabolism to slow.

a. Cells filled with clinkers become senescent and slow function; e.g., neuron conduction velocity slows in advanced age

4. The loss of the telomeric caps of chromosomes prevent the cell from conducting mitosis.

            a. Part of the telomere is eroded with each mitotic division.

b. Cancer cells are immortal as long as they are maintained: they make an enzyme called telomerase that rebuilds telomeres.                                           

Self Test

Matching I

___1. Viruses are not alive because they do not have metabolism or organelles. The rule being applied to make this conclusion is the ________?	a. ATP
___2.  This compound dissolves among the fatty acid tails of the cell membrane:	b. absorb food
___3. Fatty acid tails are nonpolar and _____?	c. K^+
___4. A _____ is combined with a gated transport channel.	d. rough endoplasmic reticulum
___5. The energy used for passive transport is _______?	e. hypotonic
___6. The energy expend by cells to do active transport is _____?	f. Na^+
___7. The process of moving glucose through glut-4 channels is _____?	g. isotonic
___8. Normally cells have high concentrations of this cation:	h. cell theory
___9. Intracellular fluids are always _____ relative to distilled water.	i. pericentriolar cloud
___10. Extracellular fluids have a high concentration of the cation ____?	j. facilitated diffusion
___11. Severe dehydration can be relieved by administering a slightly _____ IV solution.	k. kinetic
___12. Normal saline is always _____ to the blood.	l. Golgi
___13. Pinocytosis serves to ________?	m. hydrophobic
___14. Phagocytosis in our tissues is used to control ______?	n. hypertonic
___15. Preproinsulin first appears here:	o. cholesterol
___16. Proinsulin collects here:	p. bacteria
___17. Microtubules form here:	q. receptor

Matching II

Match the regional and directional terms for human unless specified.

___1. Lysosomes fuse with a food vacuole to _____?	a. polar
___2. The absence of a lyosomal or peroxisomal enzyme will result in a(n)	b. airway obstruction
___3. A mitochondrial cytopathy is always is _______?	c. dynein arms
___4. These may be coated with motor proteins:	d. increases gene assortment
___5. When cilia are absent or non-functional, this happens:	e. RNA polymerase
___6. ____have the 9+0 pattern of microtubules:	f. empty powerful digestive enzymes
___7. The microtubules of cilia and flagellae have ______?	g. testosterone
___8. Mutating genes that make the motor proteins of flagellae would result in ______?	h. synapsis
___9. The ratcheting _____  microtubules are responsible for the increase in diameter of a dividing cell.	i. inherited from mother
___10. Chromosome pair  #21, would be called _________?	j. oncogene
___11. The reduction division occurs in _______.	k. transfer RNA
___12. Genes cross over from a maternal strand to a paternal strand just after this step in the prophase of meiosis I.	l. microtubules and vesicles
___13. The advantage of sexual reproduction over sexual reproduction is that it ______ of the offspring.	m. centrioles
___14. Transcription requires _____  binding to the sense strand of DNA..	n. infertility
___15. This molecule carries one amino acid to the ribosome:	o. Meiosis I
___16. This is a mitogen for prostate cancer:	p. storage disease
___17. If a virus mutates DNA, the result can be a _________?	q. autosomes

Multiple choice

____1. Which of the processes below would be negatively affected by an increase in the volume of a cell?
        a. diffusion
        b. active transport
        c. facilitated transport
        d. osmosis
        e. Trick question alert! All the processes above would be negatively affected.

____2. As compared to eukaryotic cells, prokaryotic cells are different in which way?
        a. Bacterial flagellae don’t have microtubules.
        b. A nucleus is absent.
        c. Ribosomes are absent.
        d. DNA is absent.
        e. a and b are correct.

____3. The cell membrane compound that can be dissolved in water and fat at the same time is ____?
        a. cholesterol
        b. phospholipid    

        c. fatty acid tail
        d. polar protein
        e. All of the statements are correct.

___4. Water molecules passively move toward:
        a. hypotonic solutions
        b. higher concentrations of water
        c. higher concentrations of solutes
        d. area of higher kinetic energy
        e. All of the statements are correct.

____5. In order to encourage the movement of urea out of a kidney dialysis patient's blood, this is used.
        a. a slightly hypotonic bath solution
        b. a perfectly isotonic bath solution
        c. a slightly hypertonic solution
        d. a hypertonic IV solution
        e. an isotonic IV solution

___6. When active transport occurs, this can result:       

        a. Molecules or particles can be moved to an area of higher concentrations of that molecule.
        b. The cell must make more ATP.
        c. High energy phosphate bonds are needed to change the shape of a pumping system in the cell membrane.
        d. Small ions can be moved from an area of low concentration to a high concentration area.

        e. All of the statements are correct.

___7. Macrophages can move like an amoeba in tissues using this process:
        a. sol-gel reversal

        b. ratcheting of myosins against actins
        c. Extension of pseudopodia.
        d. Expending ATP.
        e. All of the descriptions are correct.

___8. Which statement about the cell cycle is incorrect?
        a. The chromosome content of G1 of a skin cell is 46s.
        b. 46s à 46d in the s phase.       

        c. A dividing liver cell enters prophase with 46d chromosomes.
        d. The cell spends most of its time in mitosis.
        e. Trick question alert! All of the statements are correct.

___9. Double chromosomes split in this phase of mitosis:

            a. prophase

            b. metaphase

            c. anaphase

            d. telophase

            e. s phase

___10. Which statement is incorrect concerning meiosis?

        a. The chromosome number is reduced by 1/2 in the second division.

        b. A secondary oocyte in prophase has 23 double chromomes.
        c. Crossing-over occurs in prophase I.

        d. A secondary oocyte divides mitotically.
        e. A spermatogonium can divide mitotically.

___11. Which statement concerning sex cell formation is correct?

            a. The two cell divisions of spermatogenesis are unequal.

            b. The two divisions of oogenesis are equal.

c. Polar bodies remove excess chromosomes.

d. Spermatogonia can only do meiosis.

e. One primary oocyte can make 4 mature ova.

 ___12. Tay-Sachs disease is an inherited storage disease involving a(n):
        a. mutation of the genes that produce one lysosomal enzyme
        b. treatment by supplying the missing enzyme, thereby reversing the vegetative state
        c. mitochondrial cytopathy
        d. storage disease of peroxisomes
        e. All of the descriptions are correct!

___13. Self-replicating genes can be found here:
        a. nucleus

        b. mitochondrion

        c. messenger RNA
        d. c only is correct.
        e. a and b are correct.

___14. Which statement concerning transcription is incorrect?

            a. Only one strand of the RNA double helix is transcribed.

            b. Messenger RNA codons are formed from DNA triplets.

            c. It occurs in the nucleus.

            d. There is no thymine in RNA.

            e. RNA polymerase forms mRNA.

___15. Which statement concerning translation is incorrect?

            a. It occurs at the ribosome.

            b. The amino acids must be charged with energy before they can make peptide bonds.

            c. The reciprocal of the mRNA codon AAA on a transfer RNA is TTT.

            d. The transfer RNA is partly double stranded.

            e. There are 61 types of tRNA.

___16. Microtubules are best described as:

            a. a polymer of tubulin proteins.

            b. producing the ratcheting that results in muscle cell contractions.

            c. always occurring in a 9+0 pattern or 9+2 pattern.

            d. a multimer of tubulin polymers.

            e. providing an unchanging lattice support for a cell.

___17. Ribosomes are made in the _____ (best answer)?

            a. nucleus

            b. nucleolus

            c. rough endoplasmic reticulum

            d. Golgi

            e. mitochondrion

____18. Which organelle is self-replicating?

            a. nucleus

            b. mitochondrion

            c. chloroplast of a plant cell

            d. peroxisome

            e. Trick question alert! All of these are self-replicating organelles.

____19. Which statement concerning nicotine is incorrect?

        a. Nicotine paralyses cilia.

        b. Nicotine is a mutagen.

        c. Nicotine increases the rate of mitosis of certain tissues.

        d. Nicotine is not a carcinogen.

        e. Nicotine can increase the number of mistakes in replication retained by cells.

___20. Cancer cells are like embryonic cells in which way?
        a. rate of mitosis is higher than cells of adult organs
        b. cells can migrate to new locations
        c. cancer cells do not have telomeres
        d. c only is correct.
        e. a and b are correct.

True or False

___1. The best reason why viruses are not considered to be cells is that they have no metabolism outside a host cell.
___2. The random movement of molecules can result in a purposeful movement.
___3. The movement of water molecules towards a hypertonic solution is a directed, active process.
___4. A semipermeable membrane is required for the diffusion of oxygen.

___5.  The only function of a peroxisome is to make oxygen from peroxides.

___6. It is normal for cells with gene mutations to undergo apoptosis.

___7. There are 92 chromosomes in a liver cell in the anaphase of mitosis.
___8. There are viral genes in our chromosomes.
___9. Gene mutations result after each exposure of skin to the sun, but are usually repaired.
___10. The mutations of autosomal, structural genes causing the absence of an enzyme must be inherited from both parents.
___11. Nicotine can indirectly produce mutations by speeding up mitosis.

___12. A single mutation of a structural gene usually produces cancerous cells.

___13. When a few surgeons declare, "We got it all," after a malignant tumor is removed, there are no cells cancer cells remaining.

___14. Cancer cells will live forever if fed and cleaned in cultures.

Questions to Ponder 1.4

1. If bacteria can divide every 20 minutes, starting with one Salmonella (food poisoning) bacterium, how many would be present in your small intestine in 12 hours, assuming none die during that time?

2. For the following stages of mitosis and the cell cycle, fill in the correct number of chromosomes. Designate each set as 46 d or 46 s (double or single) as for a human skin cell. Remember to count chromosomes, count centromeres.

Prophase: _____46d________
Metaphase: ___ 46d________
Anaphase: ___   (92s) (2 groups of _46s_ and _46s_ chromosomes)
Telophase: ____46s________ (as above, in each potential daughter cell)
G ₁ : _________46s________
s: _______46sà 46d_______
G ₂ : _________46d________
Prophase: _____46d________

3. For the following human spermatogonium and the spermatocytes derived from it, designate the chromosome numbers (d
or s) for each stage.

Prophase I: ____46d_______(Primary Spermatocyte)
Metaphase I: ___46d_______(Primary Spermatocyte)

Metaphase I: ___23d_+ 23d__(23d in each secondary spermatocyte to be)
Telophase I: ___ 23d_+ 23d__ (in each daughter cell to be)
Prophase II: ____23d_______ (Secondary Spermatocyte)
Metaphase II: __ 23d_______ (Secondary Spermatocyte)
Anaphase II: ___23s + 23s__(in each daughter cell to be)
Telophase II: ___23s + 23s _ (in each daughter cell to be)
Mature Sperm Cell: __23s___
Mature Ovum: ______23s __
Zygote = Sperm # + Ovum # = _____46s______(G₁ cell cycle phase of zygote)

4. What would happen to the chromosome number of your great grandchildren if meiosis did not occur? Chromosomes would double in each succeeding generation. Liver cells that have 92 chromosomes (4n, polyploidy) cannot do mitosis.

5. Explain the following statement: "Mitochondrial cytopathies are always passed from mother to child."  Since mitochondria are only donated by an oocyte, they are of maternal origin. Mutations to mitochondrial DNA are passed to both male and female offspring. Males, however, cannot pass this defect to their children because sperms do not donate mitochondria to a zygote

Answers to Questions for Appendix A

Critical Thinking 

1. Criticize the term "bad cholesterol" for LDLs. First a low density lipoprotein is a carrier of neutral fat and cholesterol, like a passenger in a car, the person is only a small part of the whole carrier. Let's not confuse the carrier with what is carried in it. LDLs are good in that they carry fat and cholesterol to cells. A good example of this function is the transport of cholesterol to the cells that make the lens capsule in the eye. LDLs that contain cholesterol can also be taken in by liver cells and be partly excreted in bile. LDLs are only bad when there is an excess of this form of lipoprotein carrier together with a low level of the HDL scavengers of oxidized cholesterol. The real puzzle is why macrophages ingest LDLs and crawl into lesions in the internal layer of arteries. Could it be because the LDLs contain oxidized cholesterol? If there is "bad cholesterol," it is the oxidized cholesterol that occurs in atherosclerotic plaque.

 2. Explain the relationship between cigarette smoking and cancer in the lung and colon. Only indirectly can nicotine contribute the gene mutations that cause cancer. There is no evidence that nicotine can mutate DNA molecules. However, it can speed up cell division and indirectly cause mutations arising my mistakes in replication. It can increase the rate of mitosis of mutated cells. Thereby, it increases the rate of growth of tumors. The relationship of using any kind of tobacco to gene mutations could from the benzopyrenes and other mutagenic chemicals produced by the roasting and combustion of tobacco.

3. Who contributes more genes to a male offspring, mom or dad or are the contributions the same? Explain your answer. When a sperm cell fertilizes an oocyte, it contributes 23 single chromosomes to combine with the oocyte's 23s chromosomes. The oocyte is much larger than the sperm that fertilizes it: the difference in size is much like a person standing by a small house. For a male child, the oocyte contributes the larger X chromosome and the sperm cell the much smaller y chromosome. So, the mother of a male child contributes more chromosomal genes to a male offspring. Secondly, there are 1000-2000 mitochondria in the oocyte, each one containing a small loop of DNA. All mitochondria come from the mother. Third, there are many mRNA copies of genes in the oocyte previous to fertilization. Therefore, contrary to "common sense," mom contributes more genes to her male child and although the contributions by mom and dad of chromosomal genes to a female (X-X) child are equal, the mother still holds an edge.

4. Why is cancer more prevalent in older people?  Similarly, why has cancer increased generally in all age groups over the 20th century? As people advance in age they accumulate mutations that have occurred due to environmental exposure to mutagenic radiation, chemicals ad viruses. Also they accumulate mutations arising from the mistakes in replication that for some reason have not been repaired. So, increased age is a risk factor for developing  cancer. Cancer has generally increased because 1.) people are living longer,  2.) many exotic, mutagenic chemicals have been released into our environment that our cells have not been equipped by design or evolution to detoxify; and 3.) exposure to radiation from open-air nuclear bomb tests, radio-imaging and radiation therapy treatments.

Questions to Ponder 1.1

 1. Do a little research and see if you can find diseases of the following membrane channels: (see http://www.neuro.wustl.edu/neuromuscular/mother/chan.html)

a. Epithelial chloride channels. The epithelial chloride channel is an ATP-activated, gated channel. If the maternal and parental genes that produce the gate protein are mutated (we know that the amino acid phenylalanine is missing from the gate protein and the DNA triplet of the gene, specifically CTT, has been deleted), the gate remains open and lets chloride leak out. Cl^- is normally more concentrated inside the plasma membrane. The chloride attacks water and the mucous secretion become thick, plugging up airways and the pancreatic ducts.

b. Potassium channels in heart tissue. The electrocardiogram will be abnormal (lengthened Q-T) and heart failure may result from mutations of the genes that produce the proteins of the Na-K-ATP-ase pump or the KCNJ2 pump protein.

c. Potassium channels in neurons. As above, Andersons Syndrome results in periodic paralysis. Several mutations substitute amino acids that are not normally found in the pump protein.

2. Do a little research and see if you can find diseases of the following receptors:

a. Androgen receptors (absent). Testicular feminization or complete androgen (testosterone and its metabolite DHT) insensitivity syndrome produces an x-y person who looks like a female. The mutant gene occurs on the male's only x-chromosome. As a result, the baby is born looking like a female externally and the condition may go unnoticed until the patient complains to a physician that she has not had a menstrual period. An examination will reveal a short vagina, no cervix or uterus, and undescended testes. Undescended testes will not do meiosis due to the higher temperature inside the abdomino-pelvic cavity. An interesting aspect of CAIS is that the testosterone secreted by the testes acts as an estrogen, hence the normal female appearance.

b. Growth hormone releasing hormone (loss of function). Growth hormone deficiencies cause short stature or pituitary dwarfism. One mutation to the pair of genes that produce growth hormone releasing hormone(GHRH) receptors in the brain prevents the full functioning of the GHRHR receptors. This means that the pituitary cannot release adequate amounts of growth hormone.

c. Follicle stimulating hormone in females (absent). Similarly, mutating the genes that produce gonadotropin realeasing hormone (GnRH) receptors will cause hypogonadism and infertility in both sexes. Following a signal from GnRH, the pituitary releases FSH that causes sperm and ova formation. Also, pituitary LH causes the secretion of male and female sex hormones that stimulate sex organ development.

_______________________________________     

Questions to Ponder 1.2

1. If you have seen the classic movie, "The Blob," why can't single cells be as large as trucks?  Single large cells, the size of "the blob," would have too much volume to support with gas exchange unless it had a special gas exchange organ and a circulation. Of course, the blob came from outer space, so maybe it did not do gas exchange!

2. Explain how, in a sedentary person, a diet high in calories, simple carbohydrates, animal fat and salts contribute to the increase of diabetes mellitus seen in the U.S. and Canada. Simple carbohydrates like glucose and made to "burn" or the excess is converted to fat and stored. The dangers of eating too much food that suddenly increase glucose levels in the blood is that it requires sudden increases in insulin production and release. The principal cause of type 2 diabetes mellitus is hyperinsulinemia that in turn causes insulin resistance (receptor downregulation). Obesity is the sign of the excessive ingestion of simple carbohyrdrates accompanied by a lack of exercise. By the way, the simplest way for most people to lose weight is to increase their level of activity.

3. Explain what would happen to blood pressure if the osmotic proteins, the albumins, were depleted by liver failure. Removing an important solute from the blood will cause water to flow out towards tissues where the solute concentration is higher and the water concentration lower. Edema or swelling results and fluid will accumulate in the abdominal cavity (ascites).

4. Why do all human cells have a Na-K-ATP-ase pump? The plasma membrane carries a normal negative change or polarity just inside the membrane relative to just outside the membrane. Potassium is several hundreds times more concentrated inside cells than in blood plasma. Inside cells, it attracts water molecules. Some speculate that element of the cytoskeleton bind potassium ions and the potassium ions bind water molecules.  Since our cells are presumed to have evolved in oceans and oceans have a high concentration of sodium and a low concentration of potassium, then the Na-K-ATP-ase pump helps to maintain the proper concentration of those ions inside cells. There are other active transport channels dedicated to transporting potassium ions to assist in concentrating potassium inside cells.  Since extracellular fluids are high in sodium, it could be said that our cells carry their own ocean around them.

---------------------------------------------

Questions to Ponder 1.3

1. An antibiotic, rifampicin, binds to the ribosomes of bacteria irreversibly. Would the bacterium die immediately? Describe the processes in the bacteria that would be affected. Bacterial ribosomes are somewhat different chemically than human ribosomes. When the antibiotic rifampicin binds to bacterial ribsomes, this stops the synthesis of structural, regulatory and enzymatic proteins. Since enzymes are responsible for metabolism and structural proteins must be replenished, particularly in fission, the bacterial cell will slowly die from a lack of energy and nutritional resources.

2. The organism that causes amoebic dysentery moves by extending itself and can be observed with red blood cells inside it. Describe its movement and what happens to the red blood cells. Endamoeba histolytica moves  by extending on large pseudopod. When the plasma membrane of the pseudopod comes into contact with a RBC, the RBC is engulfed into a membrane covered food vesicle (phagocytosis/endocytosis). Lysosomes merge with the "food" vesicle to empty their enzymes. The proteins and membranes of the cell are digested.  An exocytic vacuole will empty waste materials.

3. Describe a storage disease involving glycogen. Glycogen storage diseases occur when the starch glycogen cannot be broken down in liver and muscle tissues. Inherited deficiencies of one of the enzymes needed to break down glycogen into glucose are the causes of Cori's, Pomke and von Gierke's diseases. The general symptoms are hypoglycemia, muscle weakness and liver enlargement.

Questions to Ponder 1.4

1. If bacteria can divide every 20 minutes, starting with 2 Salmonella (food poisoning) bacteria, how many would be present in your small intestine in 7 hours, assuming none die during that time? The calculation is 2²¹ = 2,097,152 - enough to make you very ill.

2. For the following stages of mitosis and the cell cycle, fill in the correct number of chromosomes. Designate each set as 46 d or 46 s (double or single) as for a human skin cell. Remember to count chromosomes, count centromeres.

Prophase: _____46d________
Metaphase: ___ 46d________
Anaphase: ___   (92s) (2 groups of _46s_ and _46s_ chromosomes)
Telophase: ____46s________ (as above, in each potential daughter cell)
G ₁ : _________46s________
s: _______46sà 46d_______
G ₂ : _________46d________
Prophase: _____46d________

3. For the following human spermatogonium and the spermatocytes derived from it, designate the chromosome numbers (d
or s) for each stage.

Prophase I: ____46d_______(Primary Spermatocyte)
Metaphase I: ___46d_______(Primary Spermatocyte)

Metaphase I: ___23d_+ 23d__(23d in each secondary spermatocyte to be)
Telophase I: ___ 23d_+ 23d__ (in each daughter cell to be)
Prophase II: ____23d_______ (Secondary Spermatocyte)
Metaphase II: __ 23d_______ (Secondary Spermatocyte)
Anaphase II: ___23s + 23s__(in each daughter cell to be)
Telophase II: ___23s + 23s _ (in each daughter cell to be)
Mature Sperm Cell: __23s___
Mature Ovum: ______23s __
Zygote = Sperm # + Ovum # = _____46s______(G₁ cell cycle phase of zygote)

4. What would happen to the chromosome number of your great grandchildren if meiosis did not occur? Chromosomes would double in each succeeding generation. Liver cells that have 92 chromosomes (4n, polyploidy) cannot do mitosis.

5. Explain the following statement: "Mitochondrial cytopathies are always passed from mother to child."  Since mitochondria are only donated by an oocyte, they are of maternal origin. Mutations to mitochondrial DNA are passed to both male and female offspring. Males, however, cannot pass this defect to their children because sperms do not donate mitochondria to a zygote.

 Matching I
        1. h
        2. o
        3. m
        4. q
        5. k
        6. a
        7. j
        8. c
        9. n
        10. f
        11. e
        12. g
        13. b
        14. p
        15. d
        16. l

        17. I

Matching II
        1. f
        2. p

        3. i

        4.  l

        5. b

        6. m

        7. c

        8. n

        9.  a
        10. q
        11. o
        12. h
        13. d
        14. e
        15. k

        16. g

        17. j

Multiple Choice

        1. e
        2. e
        3. b
        4. c
        5. c
        6. e
        7. e
        8. d
        9. c
        10. a
        11. c
        12. a
        13. e
        14. a
        15. c
        16. d

        17. b

        18. e

        19. b

        20. e

True or False

        1. T
        2. T
        3. F
        4. F
        5. F
        6. T
        7. T
        8. T
        9. T
        10. T
        11. T
        12. F
        13. F

        14. T

Email: john.aliff @ gpc.edu